Ketosis Isn’t Always Great
A lot of people seem to be worried about carbs and getting kicked out of ketosis. A LOT. I talked about why staying in ketosis doesn’t matter a whole lot in the past for normal weight loss, but there are a few things I haven’t emphasized on. One main thing that gets me worked up is when people ask if something will knock them out of ketosis or whether a food is “compatible” with a ketogenic diet. The straight answer is that nearly everything you eat will kick you out of ketosis. You read that right. Everything.
It doesn’t matter what you eat on a ketogenic diet because anything you eat will inhibit ketogenesis. And that’s probably a good thing overall, especially when it comes to weight loss.
A little background on the graphicabove: Cotter’s paper does a very good job of explaining ketogenesis and the physiological mechanisms and responses associated with ketonemia. I highly recommend reading it.
The enzyme in the green box is HMG CoA Synthase, the enzyme that is typically referred as the rate limiting enzyme for the production of all ketones in humans. This enzyme is foremost upregulated by glucagon, as shown by the purple arrow. This is good, as glucagon is secreted by the pancreas during times of starvation and exercise (and to a lesser extent, low-carb diets and general caloric restriction), which are periods where the body needs that extra energy from fuel. Since fatty acids cannot typically provide the quick energy bursts that glucose can, nor be broken down as rapid and efficiently, this leaves the need for a slightly more efficient fuel: ketones.
Insulin inhibits this process by several mechanisms, most notably by decreasing lipolysis and activity of HMGCS2.
And it’s pertinent to point out that almost anything you eat will induce some form of insulin response. There isn’t much data I can find on fats, but it’s common knowledge that carbohydrates produce an insulin response, though protein also induces an insulin response as well. It’s been established that the magnitude and duration of the insulin response varies among foods (carbs seem to have longer duration and shorter magnitude, protein foods have the opposite). Additionally, it’s been shown that protein-only meals have a greater area under the curve, meaning the total amount of insulin produced in that time frame is greater than during carbohydrate ingestion.
Overall, though, this is probably a good thing. Ketones, like many other molecules in the body, are probably very potent messengers and can produce pretty significant effects on several important mechanisms of the body (e.g. ROS production).
But what’s important here is that excess ketone concentration in the blood can cause fat oxidation to be inhibited. High amounts of ketones slow down the ability to burn fat and will decrease metabolism. This is done through the HCA2 (or, HCAR2 in the diagram below) receptor on adipose cells. If you ask me, this is probably to avoid ketoacidosis and death, which overall would be counterproductive of the increase in ketogenesis due to the body trying to survive during starvation; just speculation, though.
I show the mechanisms above, but they aren’t important. The takeaway here is this:
- Ketones can be good. Presence of ketones show a degree of fat oxidation (particularly a benefit when losing weight), and they may play other roles in health.
- Too many ketones will slow down fat metabolism. Probably as a feedback mechanism to avoid ketoacidosis and death.
- Low amounts of ketones are indicative of fat burning, and probably mean that the body is also breaking down ketones to use as energy. This is probably optimal during ketogenic dieting.
- Almost any food will inhibit ketogenesis via insulin. It doesn’t matter if it’s carbs, protein, (or to a much lesser extent) fats. This is probably why too much protein can compromise a medical ketogenic diet.
